Lipid-conjugates having a pharmacological activity of inhibiting the enzyme phospholipase A2 (PLA2, EC 3.1.1.4) are known in the prior art. Phospholipase A2 catalyzes the breakdown of phospholipids at the sn-2 position to produce a fatty acid and a lysophospholipid. The activity of this enzyme has been correlated with various cell functions, particularly with the production of lipid mediators such as eicosanoid production (prostaglandins, thromboxanes and leukotrienes), platelet activating factor and lysophospholipids.
Glycosaminoglycans (GAG) are macro-molecules that protect the cell membrane from attacks or stimuli by a multitude of extra-cellular agents such as: Free radicals (ROS), exogenous PLA2, interleukins and other inflammatory mediators, allergens, growth factors, and degrading enzymes or invasion-promoting enzymes (e.g., heparinase, collagenase, heparanase, hyaluronidase). GAG enrichment assists in protecting cells from damage.
Since their inception, lipid-conjugates have been subjected to intensive laboratory investigation in order to obtain a wider scope of protection of cells and organisms from injurious agents and pathogenic processes.
Allergic rhinitis (AR) is an allergen-induced inflammation of the membranes lining the nose. Exposure to the allergen in AR stimulates the release of histamine and other inflammatory mediators, which cause a collection of symptoms, including nasal congestion, rhinorrhea, frontal headache, post-nasal drip, sneezing, nasal itch, itching in the ears or palate, and cough.
Allergic rhinitis is one of the most common global chronic diseases, affecting at least 10% to 25% of the population and its prevalence is increasing. Symptoms of AR can cause fatigue, headache, cognitive impairment and other systemic symptoms and may significantly impact a patient's quality of life. Appropriate management of AR may also be an important component in effective management of coexisting or complicating respiratory conditions, such as asthma, sinusitis, or chronic otitis media.
Among the goals of allergy treatment is to prevent the release of inflammatory mediators and thereby mitigate the symptoms associated with inflammation. Current treatment approaches for AR involve a step-wise approach dependent on the frequency and severity of symptoms. The most common treatments include H1-antihistamines, decongestants, mast cell stabilizers (cromones), anticholinergics, antileukotrienes, and intranasal corticosteroids (INS); these treatments vary in both mechanism and effectiveness.